Aspirin is one of the most widely used medications in the world today, with an estimated 40,000 tonnes consumed each year. Aspirin use has only grown in the past decade due to its second career in heart attack and stroke prevention. In 2002, The U.S. Preventive Services Task Force (USPSTF) concluded that aspirin’s benefit outweighed its risk in patients at high risk for coronary heart disease, and strongly suggested that clinicians discuss aspirin with adults who are at increased risk for coronary heart disease.

ASA as primary prevention

The use of aspirin in secondary prevention raised an interest in its potential use in primary prevention, that is in men and women without known heart disease.1 Alarmingly, large numbers of people have been self-administering an aspirin a day for years, in hopes of keeping heart attack away. Not enough emphasis has been placed on aspirin’s potential to do harm, especially in healthy patients.

Recently, several studies have questioned the use of aspirin in primary prevention of heart attack and stroke. A study involving 39,876 initially healthy women 45 years or older receiving 100 mg aspirin and monitored for 10 years for occurrence of first cardiovascular event showed that aspirin use lowered the risk of stroke by 17% (RR 0.83, 95% CI 0.69-0.99 p = 0.04), and had no effect on the risk of MI or death (RR 1.02, 95% CI 0.84-1.25, p = 0.83). But GI bleeding requiring transfusion was more frequent in the aspirin group than in placebo (RR 1.40, 95% CI 1.07-1.83, p = 0.02).2

A 2009 meta-analysis from the Oxford Antithrombotic Treatment Trialists’ Collaboration (ATT) also concluded that while aspirin use for primary prevention may reduce the risk of nonfatal ischemic events (0.51% aspirin vs 0.57% control per year, p = 0.0001), the risk of major gastrointestinal and extracranial bleeds were increased with aspirin (0.10% vs 0.07% per year, p < 0.0001), leading to no net effect on vascular mortality.3 The net effect on stroke was not significant (0.20% vs 0.21% per year, p = 0.4: hemorrhagic stroke 0.04% vs 0.03%, p = 0.05; other stroke 0.16% vs 0.18% per year, p = 0.08). Further trials are in progress.

Current data suggests that the number needed to treat (NNT) to prevent one cardiovascular event is 333 in women and 270 in men and the number needed to treat to cause a harm (NNH) of a bleeding event is 400 in women and 303 in men.4

The diabetes connection

Diabetics are considered at high risk for cardiovascular events and most society guidelines recommended aspirin for primary prevention in this group of patients. The use of aspirin for prevention of CVD in diabetics or peripheral arterial disease (PAD) remains unclear. In a meta-analysis conducted by Nicolucci, De Berardis and colleagues, they found no statistically significant differences in the risk of major cardiovascular events, cardiovascular mortality, all-cause mortality, MI, or stroke, and “inconsistent” evidence of harm from aspirin use. In an analysis by sex, aspirin in men appeared to significantly reduce the risk of MI by 43%, but no significant reduction in MI was seen in women.5 Also in patients with PAD, treatment with aspirin alone or with dipyridamole resulted in a statistically nonsignificant decrease in the primary end point of cardiovascular events and a significant reduction in nonfatal stroke.6 Ongoing studies — A Study of Cardiovascular Events in Diabetes (ASCEND) and the Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D) may be able to shed more light on this issue.

Focus on the risks

The tide has shifted against aspirin in primary prevention although it’s still well established in the secondary prevention of cardiovascular disease.7 The benefits of aspirin in primary prevention are fairly uncertain at this point and it’s important to ask if the risk of treating outweighs the benefit. Clinicians should focus on modifying the other risk factors such as cholesterol, hypertension and smoking, as addressing these has proven and substantial benefits in both primary and secondary prevention. I currently consider ASA in patients with a relatively low rate of bleeding complications whose Framingham score suggests > 10% risk of a vascular event over the next 10 years, after controlling other cardiac risk factors first. Many lower risk patients should not be on ASA.

References

US Preventive Services Task Force. Ann Intern Med 2002;136:157-60.

Ridker PM et al. NEJM 2005;352:1293-304. [PMID:15753114.

Baigent C et al. Lancet 2009;373:1849-60.

Drug and Therapeutics Bulletin 2009;47:122-5.

De Berardis G et al. BMJ 2009; DOI:10.1136/bmj.b4531.

Berger JS et al. JAMA. 2009 May 13;301(18):1909-19.

Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71-86.

Gregory P. Curnew, MD, FRCPC is Associate Professor at McMaster University in Hamilton, ON, and Director of the Coronary Care Unit at Hamilton General Hospital.

Doyin Oyelowo, MD, is a graduate of the American University of Antigua College of Medicine, and a first-year resident in family medicine at Atlanta Medical Center, Georgia.